Features: Dec. 3, 2001

Proteins—Under Pressure!

Courtesy of Shekhar Garde's Web site

Fundamental research conducted at Rensselaer on how proteins behave under high pressure is providing insights that could lead to novel engineering and biotechnology applications.

Shekhar Garde, assistant professor of chemical engineering, and his graduate student, Tuhin Ghosh, use molecular simulations to investigate effects of high pressure (~5000 atmospheres) on protein structure and the interactions that drive the folding of proteins in water.

The structure of a protein swells in water but stays relatively compact when high pressure is applied. But researchers have not been able to understand why until recently.

A protein chain consists of two types of amino acids - hydrophobic and hydrophilic. The hydrophobic particles repel water. In water-based solutions, they instinctively "hide" or fold inside the hydrophilic amino acids. The result is a unique 3-D structure for each kind of protein. The structure determines what a specific protein's function will be.

Molecular simulations in Garde's laboratory show that the key to pressure-induced swelling of proteins with water lies in the behavior of the water itself. With increasing pressure, water molecules are forced into the protein's hydrophobic interior, swelling the interior without greatly disrupting the overall conformation of the protein.

At higher pressures, the hydrogen-bonded water structure is "crushed." As a result, attractions between hydrophobic amino acids are weakened. This destabilizes the folded structure of proteins but not enough to fully unfold them.

Garde's research could provide an understanding of how deep-sea organisms survive at high pressures. It could also help develop novel bioseparation methods in which pressure replaces harsh chemicals as a means to separate valuable proteins from complex mixtures.

The research, performed in collaboration with Angel E. Garcia at Los Alamos National Laboratory, was published in the Nov. 7 issue of the Journal of the American Chemical Society. Garde also received a $35,000 grant from the ACS Petroleum Research Fund for further studies of pressure effects on proteins.